Genetic analysis has evolved and become a prevalent component in society. It is used to establish paternity, to identify individuals or human remains and conduct anthropological analysis of genetic diversity within populations and genetic distance between populations. It is used to determine susceptibility to hereditary diseases and in treatment protocols for somatic disease, such as cancer.
Molecular genetic analysis however, is almost totally dependent on analysis of deoxyribonucleic acid (DNA). DNA technology has become increasingly sophisticated, sensitive and the threshold for its use has become continually lowered. DNA technology has matured and includes such disparate technology as sequencing technology, polymerase chain reaction (PCR), microarray, and construction and use of DNA libraries. The complete sequence of many genomes has been achieved including human, primates (chimpanzee and orangutan), model organisms (mouse, rat, zebra fish, drosophila, Caenorhabditis elegans,) and pathogens. Human genomics has identified genetic structures including genes with, exons, introns, and promoter regions and other coding regions responsible for RNA structures. The genome includes non-coding DNA including long interspersed nuclear elements (LINEs), short interspersed nuclear elements (SINEs), retrovirus-like elements and DNA transposon copies. It also includes chromosomal structures such as centromere and telomere-specific sequences.
DNA also exists in mitochondria. This DNA contains fundamental differences to nuclear DNA, it is circular, has a different genetic code and produces only two RNAs, one in each direction, that contain the code for several genes. These features support the accepted hypothesis that mitochondrial DNA originated from endosymbiotic bacteria. The genetics of mitochondrial DNA are matrilineal.
DNA is the basis of genetic variation, which in turn is the basis for the unique phenotype of each individual. Mutations accumulate over each generation and through recombination, independent assortment and zygote formation result in a unique combination in each individual. The variation occurs within each nucleic structure, ranging in size from single nucleotide polymorphisms (SNPs), element insertion, deletion or expansion to chromosomal duplications, deletions and inversions. As it is inherited, this variation maintains a record of an individual's genetic history.
Technology that detects and records genetic variation can provide information for several purposes. It can determine genetic relationships, such as paternity testing, confirming that an individual is descended from two given individuals. DNA can be used to confirm whether a suspect was at a crime scene. A record of unique genetic markers is also used to provide a measure of genetic diversity within a population and a measure of genetic distance between populations. It is also used to determine if an individual is a carrier for a genetic disease or is predicted to be susceptible to a genetic disease. Matching specific DNA markers with a specific inherited disease phenotype has resulted in the discovery of the specific disease genes and the role of many genes in specific disease pathways and physiological mechanisms.
Extensive efforts have been made to record and annotate the human genome and measure the full extent of genetic variation. This resulted in the human genome project and the dbSNP database (www.ncbi.nlm.nih.gov/SNP/), which records human DNA polymorphisms. Using the National Council of Biotechnology Information SNP database it is now possible to obtain the allelic frequency of each SNP in a population-specific manner.
The use of DNA has distinct limitations. If it is collected from volunteers and isolated and stored appropriately it maintains its quality and can be used indefinitely. For many applications however, DNA collection is not ideal. The backbone of DNA consists of phosphodiester bonds that are vulnerable to hydrolytic attack and oxidation. The nucleobases are susceptible to oxidation, alkylation and condensation reactions. Environmental samples from biological remains, forensic samples or anthropological material contain DNA that has not been kept in ideal conditions and is susceptible to chemical and environmental degradation, reducing the quality and integrity of the resulting data. Many applications of DNA, such as use of forensic material, are limited by the frequent absence of DNA or inability to eliminate environmental contamination.
Accordingly, methods of performing analysis on biological samples that utilized a material other than DNA to allow for the collection and preservation of biological samples in circumstances where DNA may not be present or may be degraded, which enable the investigation, establishment, or exclusion of genetic relationships at a level of precision approaching that of DNA analysis would be an improvement in the art. Such a system allowing for the determination of DNA polymorphisms in a biological sample without DNA analysis would further be an improvement in the art.